This is a phase I/II trial of an oral agent known as DFMO for treatment of high-grade squamous intraepithelial lesion. Since the only current treatment option for HSIL is surgical, the availability of an oral agent would represent an advance in therapy if effective. Also, since the lesions are often multi-focal, systemic therapy offers a 2nd major advantage. We propose a study design in which we will enroll 14 subjects initially, study them on DFMO for 6 mos & perform anoscopy at defined intervals to determine if they have shown signs of disease progression or regression. After 6 months, therapy will be discontinued and they will be followed for another period of 12 months off therapy. If anyone of the initial 14 subjects shows signs of disease remission, then another 11 subjects will be enrolled for a total of 25 subjects. The availability of the GCRC will be essential to the successful completion of these studies since all the necessary equipment is already there and subjects are accustomed to using this facility as part of the follow-up in one of the other two studies.